Optical Coherence Tomography of Retinal Degeneration in Royal College of Surgeons Rats and Its Correlation with Morphology and Electroretinography
To evaluate the correlation between optical coherence tomography (OCT) and the histological, ultrastructural and electroretinography (ERG) findings of retinal degeneration in Royal College of Surgeons (RCS-/-) rats. Using OCT, we qualitatively and quantitatively observed the continual retinal degene...
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| creator | Adachi, Kobu Takahashi, Shizuka Yamauchi, Kodai Mounai, Natsuki Tanabu, Reiko Nakazawa, Mitsuru |
| description | To evaluate the correlation between optical coherence tomography (OCT) and the histological, ultrastructural and electroretinography (ERG) findings of retinal degeneration in Royal College of Surgeons (RCS-/-) rats.
Using OCT, we qualitatively and quantitatively observed the continual retinal degeneration in RCS-/- rats, from postnatal (PN) day 17 until PN day 111. These findings were compared with the corresponding histological, electron microscopic, and ERG findings. We also compared them to OCT findings in wild type RCS+/+ rats, which were used as controls.
After PN day 17, the hyperreflective band at the apical side of the photoreceptor layer became blurred. The inner segment (IS) ellipsoid zone then became obscured, and the photoreceptor IS and outer segment (OS) layers became diffusely hyperreflective after PN day 21. These changes correlated with histological and electron microscopic findings showing extracellular lamellar material that accumulated in the photoreceptor OS layer. After PN day 26, the outer nuclear layer became significantly thinner (P < 0.01) and hyperreflective compared with that in the controls; conversely, the photoreceptor IS and OS layers, as well as the inner retinal layers, became significantly thicker (P < 0.001 and P = 0.05, respectively). The apical hyperreflective band, as well as the IS ellipsoid zone, gradually disappeared between PN day 20 and PN day 30; concurrently, the ERG a- and b-wave amplitudes deteriorated. In contrast, the thicknesses of the combined retinal pigment epithelium and choroid did not differ significantly between RCS-/- and RCS+/+ rats.
Our results suggest that OCT demonstrates histologically validated photoreceptor degeneration in RCS rats, and that OCT findings partly correlate with ERG findings. We propose that OCT is a less invasive and useful method for evaluating photoreceptor degeneration in animal models of retinitis pigmentosa. |
| doi_str_mv | 10.1371/journal.pone.0162835 |
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Using OCT, we qualitatively and quantitatively observed the continual retinal degeneration in RCS-/- rats, from postnatal (PN) day 17 until PN day 111. These findings were compared with the corresponding histological, electron microscopic, and ERG findings. We also compared them to OCT findings in wild type RCS+/+ rats, which were used as controls.
After PN day 17, the hyperreflective band at the apical side of the photoreceptor layer became blurred. The inner segment (IS) ellipsoid zone then became obscured, and the photoreceptor IS and outer segment (OS) layers became diffusely hyperreflective after PN day 21. These changes correlated with histological and electron microscopic findings showing extracellular lamellar material that accumulated in the photoreceptor OS layer. After PN day 26, the outer nuclear layer became significantly thinner (P < 0.01) and hyperreflective compared with that in the controls; conversely, the photoreceptor IS and OS layers, as well as the inner retinal layers, became significantly thicker (P < 0.001 and P = 0.05, respectively). The apical hyperreflective band, as well as the IS ellipsoid zone, gradually disappeared between PN day 20 and PN day 30; concurrently, the ERG a- and b-wave amplitudes deteriorated. In contrast, the thicknesses of the combined retinal pigment epithelium and choroid did not differ significantly between RCS-/- and RCS+/+ rats.
Our results suggest that OCT demonstrates histologically validated photoreceptor degeneration in RCS rats, and that OCT findings partly correlate with ERG findings. We propose that OCT is a less invasive and useful method for evaluating photoreceptor degeneration in animal models of retinitis pigmentosa.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0162835</identifier><identifier>PMID: 27644042</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animal models ; Animals ; Biology and Life Sciences ; Comparative analysis ; Correlation ; Degeneration ; Electroretinograms ; Electroretinography ; Epithelium ; Histology ; Medical personnel ; Medical research ; Medical societies ; Medicine ; Medicine and Health Sciences ; Morphology ; Mutation ; Optical Coherence Tomography ; Photoreceptors ; Physical Sciences ; Rats ; Rats, Transgenic ; Research and Analysis Methods ; Retina ; Retinal degeneration ; Retinal Degeneration - pathology ; Retinal Degeneration - physiopathology ; Retinal pigment epithelium ; Retinitis ; Retinitis pigmentosa ; Rodents ; Social Sciences ; Surgeons ; Tomography ; Tomography, Optical Coherence - methods ; Universities and colleges ; University graduates</subject><ispartof>PloS one, 2016-09, Vol.11 (9), p.e0162835-e0162835</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Adachi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Adachi et al 2016 Adachi et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c809t-9c1dc9af6e17c70825739dff0e4ff6d7ab635c2f5f9be4b2db6930044ddcd1c53</citedby><cites>FETCH-LOGICAL-c809t-9c1dc9af6e17c70825739dff0e4ff6d7ab635c2f5f9be4b2db6930044ddcd1c53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028068/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028068/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2104,2930,23873,27931,27932,53798,53800</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27644042$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Lewin, Alfred S</contributor><creatorcontrib>Adachi, Kobu</creatorcontrib><creatorcontrib>Takahashi, Shizuka</creatorcontrib><creatorcontrib>Yamauchi, Kodai</creatorcontrib><creatorcontrib>Mounai, Natsuki</creatorcontrib><creatorcontrib>Tanabu, Reiko</creatorcontrib><creatorcontrib>Nakazawa, Mitsuru</creatorcontrib><title>Optical Coherence Tomography of Retinal Degeneration in Royal College of Surgeons Rats and Its Correlation with Morphology and Electroretinography</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>To evaluate the correlation between optical coherence tomography (OCT) and the histological, ultrastructural and electroretinography (ERG) findings of retinal degeneration in Royal College of Surgeons (RCS-/-) rats.
Using OCT, we qualitatively and quantitatively observed the continual retinal degeneration in RCS-/- rats, from postnatal (PN) day 17 until PN day 111. These findings were compared with the corresponding histological, electron microscopic, and ERG findings. We also compared them to OCT findings in wild type RCS+/+ rats, which were used as controls.
After PN day 17, the hyperreflective band at the apical side of the photoreceptor layer became blurred. The inner segment (IS) ellipsoid zone then became obscured, and the photoreceptor IS and outer segment (OS) layers became diffusely hyperreflective after PN day 21. These changes correlated with histological and electron microscopic findings showing extracellular lamellar material that accumulated in the photoreceptor OS layer. After PN day 26, the outer nuclear layer became significantly thinner (P < 0.01) and hyperreflective compared with that in the controls; conversely, the photoreceptor IS and OS layers, as well as the inner retinal layers, became significantly thicker (P < 0.001 and P = 0.05, respectively). The apical hyperreflective band, as well as the IS ellipsoid zone, gradually disappeared between PN day 20 and PN day 30; concurrently, the ERG a- and b-wave amplitudes deteriorated. In contrast, the thicknesses of the combined retinal pigment epithelium and choroid did not differ significantly between RCS-/- and RCS+/+ rats.
Our results suggest that OCT demonstrates histologically validated photoreceptor degeneration in RCS rats, and that OCT findings partly correlate with ERG findings. We propose that OCT is a less invasive and useful method for evaluating photoreceptor degeneration in animal models of retinitis pigmentosa.</description><subject>Animal models</subject><subject>Animals</subject><subject>Biology and Life Sciences</subject><subject>Comparative analysis</subject><subject>Correlation</subject><subject>Degeneration</subject><subject>Electroretinograms</subject><subject>Electroretinography</subject><subject>Epithelium</subject><subject>Histology</subject><subject>Medical personnel</subject><subject>Medical research</subject><subject>Medical societies</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Morphology</subject><subject>Mutation</subject><subject>Optical Coherence Tomography</subject><subject>Photoreceptors</subject><subject>Physical Sciences</subject><subject>Rats</subject><subject>Rats, Transgenic</subject><subject>Research and Analysis Methods</subject><subject>Retina</subject><subject>Retinal degeneration</subject><subject>Retinal Degeneration - pathology</subject><subject>Retinal Degeneration - physiopathology</subject><subject>Retinal pigment epithelium</subject><subject>Retinitis</subject><subject>Retinitis pigmentosa</subject><subject>Rodents</subject><subject>Social Sciences</subject><subject>Surgeons</subject><subject>Tomography</subject><subject>Tomography, Optical Coherence - methods</subject><subject>Universities and colleges</subject><subject>University graduates</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9Fu0zAUhiMEYmPwBggiISG4aLFjx0lukKYyoNJQpW5waznOcZLJjYPtAH0NnhinzaYW7WLyhS37-_9zfOwTRS8xmmOS4Q83ZrCd0PPedDBHmCU5SR9Fp7ggyYwliDw-WJ9Ez5y7QSglOWNPo5MkY5QimpxGf1e9b6XQ8cI0YKGTEF-bjamt6JttbFS8Bt-GMPEnqKEDK3xrurjt4rXZ7lRah4MRvBpsDaZz8Vp4F4uuipdhXhhrQe9Vv1vfxN-M7RujTb3dMRcapLfGjlGmqM-jJ0poBy-m-Sz6_vnievF1drn6slycX85kjgo_KySuZCEUA5zJDOVJmpGiUgoBVYpVmSgZSWWiUlWUQMukKllBEKK0qmSFZUrOotd7314bx6dyOo7zBKMiQyQJxHJPVEbc8N62G2G33IiW7zaMrbmwoXwaOGGKhYJSAXlJFRRlIXCmFEhQGQ4pBa-PU7Sh3EAlofNW6CPT45OubXhtfvEUJTlieTB4NxlY83MA5_mmdRK0Fh2YYZd3VqCUFvQhaIJxuCML6Jv_0PsLMVG1CHdtO2VCinI05ec0w3mIm5NAze-hwqhg08rwTVUb9o8E748EgfHwx9dicI4vr9YPZ1c_jtm3B2wDQvvGGT2Mv9Adg3QPSmucs6Du3gMjPnbZbTX42GV86rIge3X4lnei27Yi_wCd1yUb</recordid><startdate>20160919</startdate><enddate>20160919</enddate><creator>Adachi, Kobu</creator><creator>Takahashi, Shizuka</creator><creator>Yamauchi, Kodai</creator><creator>Mounai, Natsuki</creator><creator>Tanabu, Reiko</creator><creator>Nakazawa, Mitsuru</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160919</creationdate><title>Optical Coherence Tomography of Retinal Degeneration in Royal College of Surgeons Rats and Its Correlation with Morphology and Electroretinography</title><author>Adachi, Kobu ; Takahashi, Shizuka ; Yamauchi, Kodai ; Mounai, Natsuki ; Tanabu, Reiko ; Nakazawa, Mitsuru</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c809t-9c1dc9af6e17c70825739dff0e4ff6d7ab635c2f5f9be4b2db6930044ddcd1c53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Biology and Life Sciences</topic><topic>Comparative analysis</topic><topic>Correlation</topic><topic>Degeneration</topic><topic>Electroretinograms</topic><topic>Electroretinography</topic><topic>Epithelium</topic><topic>Histology</topic><topic>Medical personnel</topic><topic>Medical research</topic><topic>Medical societies</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Morphology</topic><topic>Mutation</topic><topic>Optical Coherence Tomography</topic><topic>Photoreceptors</topic><topic>Physical Sciences</topic><topic>Rats</topic><topic>Rats, Transgenic</topic><topic>Research and Analysis Methods</topic><topic>Retina</topic><topic>Retinal degeneration</topic><topic>Retinal Degeneration - pathology</topic><topic>Retinal Degeneration - physiopathology</topic><topic>Retinal pigment epithelium</topic><topic>Retinitis</topic><topic>Retinitis pigmentosa</topic><topic>Rodents</topic><topic>Social Sciences</topic><topic>Surgeons</topic><topic>Tomography</topic><topic>Tomography, Optical Coherence - methods</topic><topic>Universities and colleges</topic><topic>University graduates</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Adachi, Kobu</creatorcontrib><creatorcontrib>Takahashi, Shizuka</creatorcontrib><creatorcontrib>Yamauchi, Kodai</creatorcontrib><creatorcontrib>Mounai, Natsuki</creatorcontrib><creatorcontrib>Tanabu, Reiko</creatorcontrib><creatorcontrib>Nakazawa, Mitsuru</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Adachi, Kobu</au><au>Takahashi, Shizuka</au><au>Yamauchi, Kodai</au><au>Mounai, Natsuki</au><au>Tanabu, Reiko</au><au>Nakazawa, Mitsuru</au><au>Lewin, Alfred S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Optical Coherence Tomography of Retinal Degeneration in Royal College of Surgeons Rats and Its Correlation with Morphology and Electroretinography</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-09-19</date><risdate>2016</risdate><volume>11</volume><issue>9</issue><spage>e0162835</spage><epage>e0162835</epage><pages>e0162835-e0162835</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>To evaluate the correlation between optical coherence tomography (OCT) and the histological, ultrastructural and electroretinography (ERG) findings of retinal degeneration in Royal College of Surgeons (RCS-/-) rats.
Using OCT, we qualitatively and quantitatively observed the continual retinal degeneration in RCS-/- rats, from postnatal (PN) day 17 until PN day 111. These findings were compared with the corresponding histological, electron microscopic, and ERG findings. We also compared them to OCT findings in wild type RCS+/+ rats, which were used as controls.
After PN day 17, the hyperreflective band at the apical side of the photoreceptor layer became blurred. The inner segment (IS) ellipsoid zone then became obscured, and the photoreceptor IS and outer segment (OS) layers became diffusely hyperreflective after PN day 21. These changes correlated with histological and electron microscopic findings showing extracellular lamellar material that accumulated in the photoreceptor OS layer. After PN day 26, the outer nuclear layer became significantly thinner (P < 0.01) and hyperreflective compared with that in the controls; conversely, the photoreceptor IS and OS layers, as well as the inner retinal layers, became significantly thicker (P < 0.001 and P = 0.05, respectively). The apical hyperreflective band, as well as the IS ellipsoid zone, gradually disappeared between PN day 20 and PN day 30; concurrently, the ERG a- and b-wave amplitudes deteriorated. In contrast, the thicknesses of the combined retinal pigment epithelium and choroid did not differ significantly between RCS-/- and RCS+/+ rats.
Our results suggest that OCT demonstrates histologically validated photoreceptor degeneration in RCS rats, and that OCT findings partly correlate with ERG findings. We propose that OCT is a less invasive and useful method for evaluating photoreceptor degeneration in animal models of retinitis pigmentosa.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27644042</pmid><doi>10.1371/journal.pone.0162835</doi><tpages>e0162835</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animal models Animals Biology and Life Sciences Comparative analysis Correlation Degeneration Electroretinograms Electroretinography Epithelium Histology Medical personnel Medical research Medical societies Medicine Medicine and Health Sciences Morphology Mutation Optical Coherence Tomography Photoreceptors Physical Sciences Rats Rats, Transgenic Research and Analysis Methods Retina Retinal degeneration Retinal Degeneration - pathology Retinal Degeneration - physiopathology Retinal pigment epithelium Retinitis Retinitis pigmentosa Rodents Social Sciences Surgeons Tomography Tomography, Optical Coherence - methods Universities and colleges University graduates |
| title | Optical Coherence Tomography of Retinal Degeneration in Royal College of Surgeons Rats and Its Correlation with Morphology and Electroretinography |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-04T20%3A46%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Optical%20Coherence%20Tomography%20of%20Retinal%20Degeneration%20in%20Royal%20College%20of%20Surgeons%20Rats%20and%20Its%20Correlation%20with%20Morphology%20and%20Electroretinography&rft.jtitle=PloS%20one&rft.au=Adachi,%20Kobu&rft.date=2016-09-19&rft.volume=11&rft.issue=9&rft.spage=e0162835&rft.epage=e0162835&rft.pages=e0162835-e0162835&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0162835&rft_dat=%3Cgale_plos_%3EA471890583%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1821097032&rft_id=info:pmid/27644042&rft_galeid=A471890583&rft_doaj_id=oai_doaj_org_article_36f60424ae8b4fe9b9a17ffecef710e4&rfr_iscdi=true |